Project Summary The present project will determine the genomic basis for evolved resistance to Beauvaria bassiana in the genetic model insect, Drosophila melanogaster. Entomopathogenic fungi, such as B. bassiana, are used in biological control of mosquito vectors of dengue fever and malaria, and of other insect pests, such as bedbugs and those that affect food security. However, mechanisms of insect resistance to fungal entomopathogens are poorly understood. Understanding resistance has additional implications for human health because of strong homology between insect and mammalian innate immune systems. An evolve and resequence approach will be applied to determine the genetic basis for evolved resistance to fungal infection in Drosophila. D. melanogaster will be artificially selected for increased resistance to B. bassiana in very large, replicated experimental populations. The pre-selection source population will be derived from a cosmopolitan sample of D. melanogaster representing common natural variation worldwide. Whole-genome sequence data will be collected from selected and control populations at multiple intermediate generations throughout the selection regime, allowing observation of the temporal trajectory of adaptive alleles. It is expected that the response to selection will primarily derive from standing genetic variation, so these allele frequency dynamics will illustrate the poorly understood soft sweep mode of adaptation in natural populations. This study will determine mechanistic factors that shape antifungal defense, including elucidation of the basis for a striking sexual dimorphism in resistance, and will serve as a general model of adaptive evolution.